Adults with Immune Thrombocytopenia (ITP) are usually treated initially with steroids. However, the great majority either do not improve or do no have a lasting response. The platelet count falls as the steroids are tapered or stopped and as a result, most patients require further therapy to maintain a hemostatic platelet count. However, there is no current consensus about the best option following steroids. The current choices consist of the medical options, more high dose steroids, rituximab (ritux), or thrombopoietic agents (TPO agents); or the surgical option, splenectomy. Prednisone leads to lasting effects in very few patients following a second course; high dose dexamethasone (dex), touted in single arm studies to have curative effects, had lasting effects in only 17% of patients in a recent comparative trial. Anti-CD20 (Rituximab, ritux) leads to initial benefit in 50% of ITP patients but3 years after treatment, it appears that only 20% of adults sustain satisfactory platelet counts. TPO agents stimulate bone marrow platelet production and multiple studies demonstrate efficacy as compared to standard /placebo. These agents clearly provide a useful therapy, but are expensive, have still unclear long-term effects, and it is believed that this treatment can never be withdrawn. As removal of the spleen is irreversible, has known medical consequences, and most patients do not wish to undergo splenectomy, we have explored combinations of medical options that may offer satisfactory alternatives. We have found that ritux in combination with dexamethasone (dex) resulted in complete remissions for one or more years in half of the patients treated in a recent pilot study. Contrary to belief, TPO agents appear to lead a sustained off treatment hemostatic platelet count in some cases, possibly via the induction of regulatory T cells (Tregs). Thus overall the goal of this proposed planning grant is to prepare for a clinical trial comparing the combination of dex with anti- CD20 to a TPO agent to see which arm leads to more patients with a lasting effect at 3 years from initial treatment. As pointed out at the NIH-sponsored State of the Science meeting in September 2009, a comparison of the best current medical therapies is urgently needed. We propose in this U34 grant to prepare for a multicenter study by having the Steering Committee form a consensus on the study protocol and interface with the U24 Resource group to gain statistical input, implement an IRB and IND, and design case report forms and other material such as a manual of procedures and to accrue the sites required to successfully complete the study.